Contact information
Type
Scientific
Primary contact
Prof J J van Hilten
ORCID ID
Contact details
Leiden University Medical Centre (LUMC)
Department of Neurology
Postzone K-05Q
P.O. Box 9600
Albinusdreef 2
Leiden
2300 RC
Netherlands
+31 (0)71 526 6065
J.J.van_Hilten@lumc.nl
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
P01.098; NTR403
Study information
Scientific title
Acronym
The BIRD study
Study hypothesis
Dystonia associated with reflex sympathetic dystrophy responds markedly to intrathecal baclofen (ITB).
Ethics approval
Approval received from the local ethics committee (Commissie Medische Ethiek) on the 2nd November 2001 (ref: P01.098).
Study design
Part one: a single blinded placebo-run-in, dose-escalation design
Part two: thereafter, in responders, an open trial
Primary study design
Interventional
Secondary study design
Single-centre
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
Reflex sympathetic dystrophy (RSD)
Intervention
Screening phase:
To evaluate the efficacy of ITB a percutaneous catheter is introduced into the lumbar subarachnoid space. All patients will start with a two-day placebo run-in, followed by a gradual titration of continuous intrathecal baclofen through an external pump. The daily baclofen dose will be increased according to a fixed schedule (200, 250, 300, 375, 450, 500, 600, 700 and 800 µg/24 hours).
Depending on the response, the duration of the screening procedure may vary from one to two weeks. If a baclofen-related side-effect occurs at a particular dose, then depending on the severity of the side-effect the pump will be stopped or adjusted to a lower infusion rate.
The outcome that is evaluated to determine if a patient will be implanted is the difference in change between Global Dystonia Severity (GDS - Visual Analogue Scale on which symptom severity is rated from zero [absent] to ten [most severe]) on ITB and placebo days.
This difference is calculated through the following steps:
1. GDSbaclo: for each ITB day the sumscore of six one-hour intervals (11.00 a.m. - 4.00 p.m.) is determined. Likewise, for the two placebo days a mean placebo-sumscore is calculated (GDSplacebo)
2. GDShome: a similar mean sumscore of six one-hour intervals of the GDS at home is determined
3. For each day the GDS change score is calculated as follows:
GDSbaclo - GDShome = GDSchangescore1, expressed in % (calculated for each ITB day)
GDSplacebo - GDShome = GDSchangescore2, expressed in % (calculated for the mean of the two placebo days)
Criteria for being a candidate for pump implantation: a greater than or equal to 25% difference between the GDSchangescore1 and GDSchangescore2 present on two subsequent days (responder).
Implantation phase:
After the screening phase a programmable pump (SynchroMed Infusion system, Medtronic INC, Minneapolis MN) for continuous ITB administration will be implanted in patients who fulfill the criteria stated above. During this phase ITB therapy will be started at a dose double the effective screening dose and will be titrated for a maximum effect over a three-month period. All implanted patients will be co-managed by the department of rehabilitation. Following implantation, severely affected patient will be referred to an in-patient rehabilitation unit. Mild to moderately affected patients will be seen in the out-patient rehabilitation unit.
Intervention type
Drug
Phase
Not Specified
Drug names
Intrathecal baclofen (ITB)
Primary outcome measures
1. GDS will be calculated separately at baseline (GDShome) and during a week at one year of follow-up. The difference between these two measurements is identified as the change from baseline in GDS at one-year follow-up (GDS1year)
2. Dystonia related Functional Limitations (DFL) are self-assessed at hourly intervals across the day using four items, addressing upper extremity function, capability of making transfers and mobility. Each item is assessed on a zero to three scale. DFL will be calculated at baseline (DFLhome) and during a week at one year of follow-up.
The difference between these two measurements is identified as the change from baseline in DFL at one year follow-up (DFL1year).
Secondary outcome measures
1. RSD related impairments
2. Activities of Daily Living (ADL) and quality of life will be assessed separately before implantation and at one-year follow-up
The difference between these two measurements is identified as the change from baseline for each score.
Overall trial start date
01/01/2002
Overall trial end date
01/01/2006
Reason abandoned
Eligibility
Participant inclusion criteria
1. All patients should fulfill the diagnostic criteria of the complex regional pain syndrome consensus report of the International Association for the Study of Pain (IASP):
1.1. Continuing pain, allodynia or hyperalgesia, in which the pain is disproportionate to any inciting event
1.2. Evidence at some time of oedema, changes in skin blood flow, or abnormal sudomotor activity in the region of the pain
1.3. No condition that would otherwise account for the degree of pain and dysfunction
2. All patients must suffer from tonic dystonia in one or more extremities, that may cause fixed postures at rest of variable severity
3. Before starting the study all patients will have received a trial with oral baclofen. Only patients with an insufficient response or dose-limiting sedative effects to oral baclofen are eligible for this study
Participant type
Patient
Age group
Not Specified
Gender
Not Specified
Target number of participants
45
Participant exclusion criteria
Does not comply with the above inclusion criteria
Recruitment start date
01/01/2002
Recruitment end date
01/01/2006
Locations
Countries of recruitment
Netherlands
Trial participating centre
Leiden University Medical Centre (LUMC)
Leiden
2300 RC
Netherlands
Sponsor information
Organisation
Leiden University Medical Centre (LUMC) (The Netherlands)
Sponsor details
Department of Neurology
P.O. Box 9600
Leiden
2300 RC
Netherlands
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Industry
Funder name
Leiden University Medical Centre (LUMC) (The Netherlands)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Medtronic Europe S.A. (Switzerland)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary